scholarly journals Mesenchymal Stem Cells in the Adult Human Liver: Hype or Hope?

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1127 ◽  
Author(s):  
Irina V. Kholodenko ◽  
Leonid K. Kurbatov ◽  
Roman V. Kholodenko ◽  
Garik V. Manukyan ◽  
Konstantin N. Yarygin
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Human Liver ◽  
Chronic Liver ◽  
Attractive Alternative ◽  
Short Supply

Chronic liver diseases constitute a significant economic, social, and biomedical burden. Among commonly adopted approaches, only organ transplantation can radically help patients with end-stage liver pathologies. Cell therapy with hepatocytes as a treatment for chronic liver disease has demonstrated promising results. However, quality human hepatocytes are in short supply. Stem/progenitor cells capable of differentiating into functionally active hepatocytes provide an attractive alternative approach to cell therapy for liver diseases, as well as to liver-tissue engineering, drug screening, and basic research. The application of methods generally used to isolate mesenchymal stem cells (MSCs) and maintain them in culture to human liver tissue provides cells, designated here as liver MSCs. They have much in common with MSCs from other tissues, but differ in two aspects—expression of a range of hepatocyte-specific genes and, possibly, inherent commitment to hepatogenic differentiation. The aim of this review is to analyze data regarding liver MSCs, probably another type of liver stem/progenitor cells different from hepatic stellate cells or so-called hepatic progenitor cells. The review presents an analysis of the phenotypic characteristics of liver MSCs, their differentiation and therapeutic potential, methods for isolating these cells from human liver, and discusses issues of their origin and heterogeneity. Human liver MSCs are a fascinating object of fundamental research with a potential for important practical applications.

scholarly journals Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Chunyang Peng ◽  
Yajiao Li ◽  
Li Lu ◽  
Jianwen Zhu ◽  
Huiyu Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Cell Therapy ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Umbilical Cord ◽  
Neural Stem Progenitor Cells ◽  
One Step

Cell therapy has emerged as a promising strategy for treating neurological diseases such as stroke, spinal cord injury, and various neurodegenerative diseases, but both embryonic neural stem cells and human induced Pluripotent Stem Cell- (iPSC-) derived neural stem cells have major limitations which restrict their broad use in these diseases. We want to find a one-step induction method to transdifferentiate the more easily accessible Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) into neural stem/progenitor cells suitable for cell therapy purposes. In this study, UC-MSCs were induced to form neurospheres under a serum-free suspension culture with Epidermal Growth Factor- (EGF-) and basic Fibroblast Growth Factor- (bFGF-) containing medium within 12 hours. These MSC-derived neurospheres can self-renew to form secondary neurospheres and can be readily induced to become neurons and glial cells. Real-time PCR showed significantly upregulated expression of multiple stemness and neurogenic genes after induction. RNA transcriptional profiling study showed that UC-MSC-derived neurospheres had a unique transcriptional profile of their own, with features of both UC-MSCs and neural stem cells. RayBio human growth factor cytokine array analysis showed significantly upregulated expression levels of multiple neurogenic and angiogenic growth factors, skewing toward a neural stem cell phenotype. Thus, we believe that these UC-MSC-derived neurospheres have amenable features of both MSCs and neural stem/progenitor cells and have great potential in future stem cell transplantation clinical trials targeting neurological disorders.

The effectiveness of autologous mesenchymal stem cells in the treatment of liver cirrhosis and the method of their visualization in the patient’s body

2020 ◽  
Vol 22 (3) ◽  
pp. 35-40
Author(s):  
I. E. Kotkas ◽  
N. I. Enukashvili ◽  
Sh. M. Asadulayev ◽  
A. V. Chubar’
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Cell Therapy ◽  
Liver Tissue ◽  
Ultrasound Examination ◽  
Test Results ◽  
Resonance Imaging ◽  
Cell Structures ◽  
Autologous Mesenchymal Stem Cells

Abstract. The effectiveness of the influence of autologous mesenchymal stem cells on the function of liver tissue in liver cirrhosis of alimentary etiology is considered, as well as the possibility of visualization of the introduced cell structures with subsequent cytological confirmation. To be able to track autologous mesenchymal stem cells introduced in the patients body, they were labeled with iron oxide nanoparticles. Visualization of the introduced cell structures was performed using magnetic resonance imaging and ultrasound examination of the liver. 6 months after the cell therapy, clinical and biochemical blood tests, lidocaine test results, elastography indicators were evaluated, and the dynamics of hepatic encephalopathy was evaluated. The effectiveness of using autologous mesenchymal stem cells was evidenced by the improvement of the above indicators. Also, 6 months after treatment, a liver tissue biopsy was performed from the sites of fixation of previously introduced cell structures. Histological examination revealed the largest number of labeled cells in the liver micro-nodes, as well as at the borders of micro-nodes and fibrous septa. The use of cell therapy in a patient suffering from liver cirrhosis of alimentary etiology helped to improve the indicators of laboratory and instrumental research methods. No complications were detected during the procedure.

SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via PI3K/Akt pathway

2020 ◽  
Author(s):  
Xiaoyi Wang ◽  
Huijiao Jiang ◽  
Lijiao Guo ◽  
Sibo Wang ◽  
Wenzhe Cheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Structure Formation ◽  
Endothelial Progenitor Cells ◽  
Hind Limb ◽  
Capillary Density ◽  
Akt Pathway ◽  
Paracrine Action

Abstract Background: Cell-based therapeutics bring great hope in areas of unmet medical needs. Mesenchymal stem cells (MSCs) has been suggested to facilitate neovascularization mainly by paracrine action, and endothelial progenitor cells (EPCs) can differentiate into mature endothelial cells. Studies have demonstrated that a combination cell therapy that includes MSCs and EPCs has a favorable effect on ischemic limbs. However, the mechanism of combination cell therapy remains unclear. Herein, we investigate whether stromal cell-derived factor (SDF)-1 secreted by MSCs contributes to. Furthermore, we examined whether SDF-1 affects EPC migration via Phosphoinositide 3-Kinases (PI3K)/protein kinase B (termed as Akt) signaling pathway.Methods: First, intramuscular MSC injections were supplemented with intravenous EPC injections in the mouse model of hind limb ischemia. The incorporation of Qdot® 525 labeled-EPC into the vasculature and capillary density was evaluated by CD31 immunohistochemistry and immunofluorescence, respectively. Then, the concentration of SDF-1 secreted by MSCs was detected via quantitative immunoassay. Flow cytometry was performed to quantify CXC chemokine receptor (CXCR) 4-positive EPCs. The effect of MSCs on EPC migration was measured by a transwell system and a tube-like structure formation on Matrigel. The SDF-1 antagonist AMD3100 and the PI3K inhibitor wortmannin were separately used to determine the participation of CXCR4 and PI3K into EPC migration. Finally, western blot assay was performed to detect the effect of SDF-1 secreted by MSCs on Akt phosphorylation in EPCs.Results: The combination delivery of MSCs and EPCs via a “dual-administration” approach enhanced the incorporation of EPCs into the vasculature and increased the capillary density in mouse ischemic hind limb. The SDF-1 concentration secreted by MSCs was 2.61 ng/ml after 48 h. CXCR4-positive EPCs increased after incubation with MSC-conditioned medium (CM). MSCs contributed to EPC migration and tube-like structure formation, both of which were suppressed by AMD3100 and wortmannin. Phospho-Akt induced by MSC-CM was attenuated when EPCs were pretreated with AMD3100 and wortmannin.Conclusions: The paracrine action of MSCs contributes to EPC migration. Furthermore, SDF-1 secreted by MSCs induces EPC migration. The mechanism of this migration is related to the activation of the Akt pathway

scholarly journals In VitroandIn VivoHepatic Differentiation of Adult Somatic Stem Cells and Extraembryonic Stem Cells for Treating End Stage Liver Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chenxia Hu ◽  
Lanjuan Li
Keyword(s):  
Stem Cells ◽  
Liver Tissue ◽  
Liver Diseases ◽  
Embryonic Stem ◽  
Somatic Stem Cells ◽  
Hepatic Differentiation ◽  
Short Supply ◽  
End Stage ◽  
Promising Source

The shortage of liver donors is a major handicap that prevents most patients from receiving liver transplantation and places them on a waiting list for donated liver tissue. Then, primary hepatocyte transplantation and bioartificial livers have emerged as two alternative treatments for these often fatal diseases. However, another problem has emerged. Functional hepatocytes for liver regeneration are in short supply, and they will dedifferentiate immediatelyin vitroafter they are isolated from liver tissue. Alternative stem-cell-based therapeutic strategies, including hepatic stem cells (HSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), are more promising, and more attention has been devoted to these approaches because of the high potency and proliferation ability of the cells. This review will focus on the general characteristics and the progress in hepatic differentiation of adult somatic stem cells and extraembryonic stem cellsin vitroandin vivofor the treatment of end stage liver diseases. The hepatic differentiation of stem cells would offer an ideal and promising source for cell therapy and tissue engineering for treating liver diseases.

scholarly journals Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy

2013 ◽  
Vol 13 (2) ◽  
pp. 120-132 ◽  
Author(s):  
Noushin Dianat ◽  
Clara Steichen ◽  
Ludovic Vallier ◽  
Anne Weber ◽  
Anne Dubart-Kupperschmitt
Keyword(s):  
Stem Cells ◽  
Cell Therapy ◽  
Pluripotent Stem Cells ◽  
Liver Diseases ◽  
Human Liver ◽  
Human Pluripotent Stem Cells

scholarly journals Implications of the immunoregulatory functions of mesenchymal stem cells in the treatment of human liver diseases

2010 ◽  
Vol 8 (1) ◽  
pp. 19-22 ◽  
Author(s):  
Hu Lin ◽  
Ruonan Xu ◽  
Zheng Zhang ◽  
Liming Chen ◽  
Ming Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Diseases ◽  
Human Liver

Placenta-derived mesenchymal stem cells for allogenic cardiac cell therapy

2012 ◽  
Vol 60 (S 01) ◽  
Author(s):  
R Roy ◽  
M Kukucka ◽  
D Messroghli ◽  
A Brodarac ◽  
M Becher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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